Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA

被引：2032

作者：

He, Yu-Fei ^{[1
]}

Li, Bin-Zhong ^{[1
]}

Li, Zheng ^{[1
]}

Liu, Peng ^{[1
]}

Wang, Yang ^{[1
]}

Tang, Qingyu

Ding, Jianping

Jia, Yingying

Chen, Zhangcheng

Li, Lin

Sun, Yan ^{[2
]}

Li, Xiuxue ^{[2
]}

Dai, Qing ^{[3
,4
]}

Song, Chun-Xiao ^{[3
,4
]}

Zhang, Kangling ^{[5
]}

He, Chuan ^{[3
,4
]}

Xu, Guo-Liang ^{[1
]}

机构：

[1] Chinese Acad Sci, Grp DNA Metab, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China

[2] Chinese Acad Sci, Inst Mat Med, Shanghai 201203, Peoples R China

[3] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[4] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA

[5] Loma Linda Univ, Sch Med, Dept Biochem, Loma Linda, CA 92350 USA

来源：

SCIENCE | 2011年 / 333卷 / 6047期

基金：

美国国家科学基金会;

关键词：

EMBRYONIC STEM-CELLS; GLYCOSYLASE ACTIVITY; GENE-EXPRESSION; 5-HYDROXYMETHYLCYTOSINE; DEMETHYLATION; METHYLATION; REPAIR; DEAMINATION;

D O I：

10.1126/science.1210944

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.

引用

页码：1303 / 1307

页数：5

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